Dovitinib (TKI-258)

For research use only. Not for use in humans.

目录号:S1018 别名: CHIR-258

Dovitinib (TKI-258) Chemical Structure

CAS No. 405169-16-6

Dovitinib (TKI-258, CHIR-258)是一种多靶点的RTK抑制剂,在无细胞试验中对III型(FLT3/c-Kit)作用最强,IC50为1 nM/2 nM,同时也作用于IV类(FGFR1/3)和V类(VEGFR1-4) RTKs,IC50为8-13 nM,但对InsR,EGFR,c-Met,EphA2,Tie2,IGF-1R和HER2作用较弱。Phase 4。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 1559.76 现货
RMB 1382.19 现货
RMB 2198.71 现货
RMB 3845.24 现货
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客户使用Selleck生产的Dovitinib (TKI-258)发表文献38篇:

产品安全说明书

FLT3抑制剂选择性比较

生物活性

产品描述 Dovitinib (TKI-258, CHIR-258)是一种多靶点的RTK抑制剂,在无细胞试验中对III型(FLT3/c-Kit)作用最强,IC50为1 nM/2 nM,同时也作用于IV类(FGFR1/3)和V类(VEGFR1-4) RTKs,IC50为8-13 nM,但对InsR,EGFR,c-Met,EphA2,Tie2,IGF-1R和HER2作用较弱。Phase 4。
特性 Dovitinib是MMRC的首要候选药MMRC, 促进多发性骨髓瘤药物研究;MMRC是汇合领先学术机构的非盈利机构。
靶点
FLT3 [1]
(Cell-free assay)
c-Kit [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)
VEGFR3/FLT4 [1]
(Cell-free assay)
FGFR3 [1]
(Cell-free assay)
1 nM 2 nM 8 nM 8 nM 9 nM
体外研究

Dovitinib有效抑制FGFR1/3和VEFFR1-2,IC50为8-13 nM。Dovitinib对InsR, EGFR, c-Met, EphrinA2, Tie2, IGFR1,和HER2抑制效果不大。Dovitinib作用于FGF刺激的野生型B9细胞和F384L突变型B9细胞的生长显示出强细胞毒性,IC50为25 nM。然而,Dovitinib作用于MINV突变型B9细胞显示出低细胞毒性。Dovitinib抑制下游ERK1/2的磷酸化作用。[1] Dovitinib作用于MV4;11 (FLT-3 ITD突变型)时比作用于RS4;11 (FLT-3野生型)显示出更高的抗恶性细胞增生的能力。[2] 另一方面,Dovitinib也选择性地抑制FGFR1癌基因配体2-FGFR-阳性的KG1和KG1A细胞系,这些细胞系有FGFR1癌基因配体2-FGFR1聚合基因。另外,Dovitinib抑制8p11骨髓增殖综合征(EMS)病人的原代细胞生长。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SupB15 NV3CWFlRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmS0TWM2OD1yLkS0PUDPxE1? NWK0VG5ZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFIxPzNpPkK1NlAzODd|PD;hQi=>
SupB15-R MnXIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYnWO49yUUN3ME2wMlU2QCEQvF2= NHPUcYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwNlA4Oyd-MkWyNFIxPzN:L3G+
BaF3-pSRα MoHpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTBwNk[4JO69VQ>? NVrUS2czRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFIxPzNpPkK1NlAzODd|PD;hQi=>
BaF3-p210Bcr-Abl NHTBNm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTBwNkmyJO69VQ>? MoWxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEKwO|MoRjJ3MkCyNFc{RC:jPh?=
BaF3-p210Bcr-Abl-T315I M3fZbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXfJR|UxRTJwNkK2JO69VQ>? NXzJSXd6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFIxPzNpPkK1NlAzODd|PD;hQi=>
CCRF-CEM MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTzO2E4UUN3ME2wMlM6QCEQvF2= Mmf4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEKwO|IoRjJ3MkCyNFczRC:jPh?=
CEM/C2 NFGzRW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDD[XBzUUN3ME2xMlEzPSEQvF2= Ml;LQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEKwO|IoRjJ3MkCyNFczRC:jPh?=
Nalm-6 Mn\uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVLQV5RqUUN3ME2wMlM5OiEQvF2= M4HnR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkCyNFczLz5{NUKwNlA4OjxxYU6=
SEM-K2 M{HzZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjJTZNKSzVyPUCuNFIzKM7:TR?= MnTCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEKwO|IoRjJ3MkCyNFczRC:jPh?=
HB-1119 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Moq4TWM2OD1yLkCyPEDPxE1? M3\2[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkCyNFczLz5{NUKwNlA4OjxxYU6=
RS4:11 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUXJR|UxRTJwOEGg{txO MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJyMkC3Nkc,OjV{MEKwO|I9N2F-
Nalm-6 NVXpV3lSSXCxcITvd4l{KEG|c3H5 NFLZOZMzKM7:TR?= NH7xPWwzPC92ODDo NY\6ZohQcW6mdXPld{BieG:ydH;zbZMhemW|dXz0bY5oKGmwIHHic5V1KDd{JTDv[kBk\WyuIHTlZZRpKGGodHXyJFI1KGhidILlZZRu\W62IHHu[EA5OSViYX\0[ZIhPDhiaB?= NE\6b289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwNlA4Oid-MkWyNFIxPzJ:L3G+
SEM-K2 NFXzTnhCeG:ydH;zbZMhSXO|YYm= NWLv[o9iOC5zL{Gg{txO NY\rZ|ZjOjRiaB?= NVfVVnlIcW6mdXPld{Bm[XKueTDhdI9xfG:|aYOgc4YhW0WPLVuyJINmdGy|IHH0JFAvOSEQvF2gZYZ1\XJiMkSgbC=> MnvRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEKwO|IoRjJ3MkCyNFczRC:jPh?=
HCT-116 NXzQe|ZiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFrKbZZKSzVyPUOuNFUxNjV6IN88US=> NXvzbZpLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVU4PTBpPkK0OFk2PzVyPD;hQi=>
HT-29 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmTTTWM2OD13LkKxMlk{KM7:TR?= MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7NUe1NEc,OjR2OUW3OVA9N2F-
SW-480 NUDzRmpmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mo\2TWM2OD12LkOzNE41PyEQvF2= MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7NUe1NEc,OjR2OUW3OVA9N2F-
CaCO2 NVTmepdST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVz0SJRGUUN3ME2zMlI{OC54NDFOwG0> NWHXc2JMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVU4PTBpPkK0OFk2PzVyPD;hQi=>
LS174T NGntSZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTRwM{OwMlQ4KM7:TR?= NYX4b|k{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVU4PTBpPkK0OFk2PzVyPD;hQi=>
HEC-1A MVPGeY5kfGmxbjDBd5NigQ>? MmXzNE4xPS9yLkGvNE42KM7:TR?= MlK0O|IhcA>? M1jLXINifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v NHHYd|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OVc2OCd-MkS0PVU4PTB:L3G+
AN3CA MojMSpVv[3Srb36gRZN{[Xl? M{nBOVAvODVxMD6xM|AvPSEQvF2= M1vyfFczKGh? MojrZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> MlzUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUW3OVAoRjJ2NEm1O|UxRC:jPh?=
MFE-296  M2\VWmZ2dmO2aX;uJGF{e2G7 Mnv2NE4xPS9yLkGvNE42KM7:TR?= MWe3NkBp MmftZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> MoHwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUW3OVAoRjJ2NEm1O|UxRC:jPh?=
UMC3 MVTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M2rQT|EuOTBizszN M3v2RlczKGh? MVLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXrHVohWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzNlU1PjFpPkK0N|I2PDZzPD;hQi=>
5637 NGL4dFBE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M17CV|EuOTBizszN MUi3NkBp NXPadng{cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN{NUS2NUc,OjR|MkW0OlE9N2F-
HU456 M{T1cWNmdGxiVnnhZoltcXS7IFHzd4F6 MWOxMVExKM7:TR?= NV:yRWkzPzJiaB?= NH;nRY5qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MlHKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|MkW0OlEoRjJ2M{K1OFYyRC:jPh?=
MGHU4 NEjyfHpE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVTzWpc4OS1zMDFOwG0> MVG3NkBp M1\pdolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NHPnN3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOyOVQ3OSd-MkSzNlU1PjF:L3G+
HT1376 NXmwfHVzS2WubDDWbYFjcWyrdImgRZN{[Xl? M2DYSFEuOTBizszN M{\qO|czKGh? MXnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MlKzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|MkW0OlEoRjJ2M{K1OFYyRC:jPh?=
RT112 MU\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MlvHNU0yOCEQvF2= Mn\QO|IhcA>? NF\zVphqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MkG1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|MkW0OlEoRjJ2M{K1OFYyRC:jPh?=
T24 NYjrTYdZS2WubDDWbYFjcWyrdImgRZN{[Xl? M4jwelEuOTBizszN NUDINFI4PzJiaB?= MWrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN{NUS2NUc,OjR|MkW0OlE9N2F-
BFTC905 MYfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NG\2RmQyNTFyIN88US=> NIWzXXE4OiCq NX34[JY2cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NX\uU|FRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzNlU1PjFpPkK0N|I2PDZzPD;hQi=>
TCC-SUP NVSxRZR4S2WubDDWbYFjcWyrdImgRZN{[Xl? MYSxMVExKM7:TR?= MmT1O|IhcA>? MVPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NGXkRXU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOyOVQ3OSd-MkSzNlU1PjF:L3G+
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HONE1 M3rsUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWmwMlEuOTBizszN MlS5OFjDqGh? NHrERYNqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NIfMdXE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEKzPFA6PCd-MkSyN|gxQTR:L3G+
HNE1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUPzNVhOOC5zLUGwJO69VQ>? NVzIcVlnPDkEoHi= M4jae4lv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> M{PQcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkO4NFk1Lz5{NEKzPFA6PDxxYU6=
CNE2  MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MofHNE4yNTFyIN88US=> Mny3OFjDqGh? MWPpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ|OEC5OEc,OjR{M{iwPVQ9N2F-
C666-1 NEfy[IJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV6wMlEuOTBizszN MVi0POKhcA>? MXXpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= M2XmNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkO4NFk1Lz5{NEKzPFA6PDxxYU6=
HeLa MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU[wMlEuOTBizszN MWiyOEBp MXTpcoR2[2W|IFeyM20h[XK{ZYP0JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ|OEC5OEc,OjR{M{iwPVQ9N2F-
Hep3B NECxOYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUCwMlEuOTBizszN MmThNlQhcA>? MU\pcoR2[2W|IFeyxsBienKnc4VCpC=> Mn\SQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{M{iwPVQoRjJ2MkO4NFk1RC:jPh?=
HepG2 NYO4OG5ET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{LIb|Q5KGh? MWLJR|UxRTJwN{K3JOKyKDBwNEK5JO69VQ>? NVnFR5JjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFY2QTFpPkKzOVQ3PTlzPD;hQi=>
Hep3B M4X2SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGHx[5I1QCCq NYDiVZNGUUN3ME20MlIzOyEEsTCwMlg{QSEQvF2= MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV2NkW5NUc,OjN3NE[1PVE9N2F-
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Huh7 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MW[0PEBp NUD3e5pXUUN3ME2xOU4xODdiwsGgO{4{OzRizszN M1XrUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUS2OVkyLz5{M{W0OlU6OTxxYU6=
HepG2 MnfuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjZO|IhcA>? NVzOWoVyUUN3ME2xMlIxOCEEsTCwMlIzPiEQvF2= MoH5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NE[1PVEoRjJ|NUS2OVkyRC:jPh?=
Hep3B MlH5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLUR2Y4OiCq NWn0fYFrUUN3ME2wMlg6OiEEsTCwMlA1PCEQvF2= NGLRbpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{W0OlU6OSd-MkO1OFY2QTF:L3G+
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Huh7 NFnPb4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Moi0O|IhcA>? MUjJR|UxRTNwOUiwJOKyKDBwOECzJO69VQ>? MmPSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NE[1PVEoRjJ|NUS2OVkyRC:jPh?=
MFE280 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWfOVHdVUUN3ME2wMlQzKMLzIECuNFYh|ryP MnizQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
AN3CA NH7NfpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1LteGlEPTB;MD61NEDDuSByLkGwJO69VQ>? MkLvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
HEC155 M1fyfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXmxbIw2UUN3ME2wMlY3KMLzIECuNFkh|ryP MoTYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
MFE296 M3G5PGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFG4ZYlKSzVyPUCuOlYhyrFiMD6xPUDPxE1? NXHveph{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
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EN1 NXrtOG9rT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLRWY5lUUN3ME2xMlAzKMLzIECuNlUh|ryP MmLZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
SNGII M3T5Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV7JR|UxRTFwMkSgxtEhOC5{ODFOwG0> NUW2elZiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
ISHIKAWA MmTIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4m5[2lEPTB;MT6zNEDDuSByLkGxJO69VQ>? M2nyWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
HEC1A NXTm[Gw6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV7JR|UxRTFwM{SgxtEhOC5|MDFOwG0> M2Dp[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
KLE MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorLTWM2OD1zLkO3JOKyKDBwMEKg{txO NHTie5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
SNGM NEHzUlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3zIe2lEPTB;MT60NkDDuSByLkGzJO69VQ>? NEDldFA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
USPC2 MkL0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIL5foNKSzVyPUGuOlIhyrFiMD6wNUDPxE1? NEC3UFU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
EN M{TnTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIL5bJhKSzVyPUGuOlYhyrFiMD6wNUDPxE1? M3HOcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
MFE319 MlnpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPGenZKSzVyPUGuPFchyrFiMD60OUDPxE1? Mmj4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
EFE184 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NI\Sd5BKSzVyPUKuNFQhyrFiMD6xN{DPxE1? NV\sXFNPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
ECC1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIqwOGtKSzVyPUKuNFchyrFiMD6wNUDPxE1? NUDhNG41RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
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USPC1 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPuTWM2OD1{Lk[wJOKyKDBwMUOg{txO MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
SPAC1L Mn3ZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoH0TWM2OD1|LkC2JOKyKDFwMUSg{txO MmnRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
HUVEC MUfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NX;VSotnOC1{NTFOwG0> M2XWTlczKGh? NYDYc2MyTE2VTx?= MnHFbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NHn2fXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{KyPFAyPyd-MkOyNlgxOTd:L3G+
HMVEC M37vPWNmdGxiVnnhZoltcXS7IFHzd4F6 NHrNTWUxNTJ3IN88US=> NVfnSow2PzJiaB?= NIHMPXVFVVOR Mnz0bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXr0WHB4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyNlgxOTdpPkKzNlI5ODF5PD;hQi=>
MHCC-97H MnT1R4VtdCCYaXHibYxqfHliQYPzZZk> MXuwMVI2KM7:TR?= MUO3NkBp Mm\LSG1UVw>? NYPkPJB6cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NVHmdVdxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyNlgxOTdpPkKzNlI5ODF5PD;hQi=>
SMMC7721 MkT6R4VtdCCYaXHibYxqfHliQYPzZZk> Mn7WNE0zPSEQvF2= NEOxbGU4OiCq MXLEUXNQ MnHObY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MmOxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{MkiwNVcoRjJ|MkK4NFE4RC:jPh?=
Huh-7 M{K1RWFxd3C2b4Ppd{BCe3OjeR?= MVqwMVEzNjVizszN Mk\oNlQhcA>? Moi3SG1UV8Li NU[1foFve2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NF\XPYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkKzNFQ4QSd-MkKyN|A1Pzl:L3G+
Sk-Hep1 MorNRZBweHSxc3nzJGF{e2G7 MV2wMVEzNjVizszN M{TkN|I1KGh? MkXtSG1UV8Li M1HwNpNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ|MES3PUc,OjJ{M{C0O|k9N2F-
Hep3B MknNRZBweHSxc3nzJGF{e2G7 NUHXZXpbOC1zMj61JO69VQ>? NI\Y[W8zPCCq NV3zXpJkTE2VT9Mg Ml;Xd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NXrWPHBVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyN|A1PzlpPkKyNlMxPDd7PD;hQi=>
PLC5 MXHBdI9xfG:|aYOgRZN{[Xl? NYrTUJFzOC1zMj61JO69VQ>? M2HkdVI1KGh? NXPCfXBOTE2VT9Mg NF\sN3Z{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ|MES3PUc,OjJ{M{C0O|k9N2F-
PLC5 NUHtNVNsS2WubDDWbYFjcWyrdImgRZN{[Xl? NV\mblY5OC1zNTFOwG0> MYK3NkBp NGjqS|Jz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MmCxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Hep3B MV3D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NYrybINCOC1zNTFOwG0> MlnYO|IhcA>? NGfOZ2xz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Sk-Hep1 NGrPOGJE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NYPKNINbOC1zNTFOwG0> MV:3NkBp Mm\ndoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Huh-7 NGTx[ZdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NFfwS4cxNTF3IN88US=> MlLxO|IhcA>? M3nuc5Jm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= M{\NW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUiwN|A5Lz5{MkG4NFMxQDxxYU6=
PLC5 NX\NWHRxSXCxcITvd4l{KEG|c3H5 NGixVXcxNTF3IN88US=> M{Xkb|I1KGh? NEfPXXJqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Hep3B M3rIXWFxd3C2b4Ppd{BCe3OjeR?= MnnNNE0yPSEQvF2= NGrEZ24zPCCq Ml7SbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M2O0RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUiwN|A5Lz5{MkG4NFMxQDxxYU6=
Sk-Hep1 MmTvRZBweHSxc3nzJGF{e2G7 NIO5PWQxNTF3IN88US=> NUm1[nMxOjRiaB?= MW\pcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? NHPkTWI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Huh-7 MVHBdI9xfG:|aYOgRZN{[Xl? NVX0dXlYOC1zNTFOwG0> M3Xwb|I1KGh? MlvwbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M3Pxc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUiwN|A5Lz5{MkG4NFMxQDxxYU6=
PLC5 NVXvRnoxTnWwY4Tpc44hSXO|YYm= MUGwMVExKM7:TR?= MWCyOEBp M1f0VoNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Hep3B M3\aNGZ2dmO2aX;uJGF{e2G7 MorENE0yOCEQvF2= M4Tnc|I1KGh? NFXP[Flk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Sk-Hep1 MXHGeY5kfGmxbjDBd5NigQ>? MX2wMVExKM7:TR?= MXSyOEBp NGfyeWRk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NWTqUI53RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxPFA{ODhpPkKyNVgxOzB6PD;hQi=>
Huh-7 Ml3CSpVv[3Srb36gRZN{[Xl? MUiwMVExKM7:TR?= MnLnNlQhcA>? NIK4TWpk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? M17JVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUiwN|A5Lz5{MkG4NFMxQDxxYU6=
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BT-37 NVjQPGJteUiWUzDhd5NigQ>? MoW4dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy| M{XZOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB-EBc1 NFTM[pFyUFSVIHHzd4F6 NYjib|MxeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM> M2P6[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
U-2 OS NVziRWNyeUiWUzDhd5NigQ>? NITje3ByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiVT2yJG9UKGOnbHzz NXHJeWdwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2 MXvxTHRUKGG|c3H5 NV[3eHBJeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=> M1m1WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH NYHPOnNxeUiWUzDhd5NigQ>? MX;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3TTEBk\Wyucx?= NEfLRm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
NB1643 M3zKd5FJXFNiYYPzZZk> M4\KeZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQkG2OFMh[2WubIO= M1;vUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5 M2m2c5FJXFNiYYPzZZk> M2D3PJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCOQV6tOUBk\Wyucx?= M2\1elxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12 NHXBWpVyUFSVIHHzd4F6 M1vhdpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?= MmHSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh18 NUT2NXoyeUiWUzDhd5NigQ>? NF;l[|VyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnixPEBk\Wyucx?= MoX4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
OHS-50 MnrEdWhVWyCjc4PhfS=> M1fNWZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO= NGjqR|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
RD MmXGdWhVWyCjc4PhfS=> NF;nNodyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUlSgZ4VtdHN? NHjaXXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
insect cells NXLYdZROTnWwY4Tpc44h[XO|YYm= MmCzNUB1dyB2IHjydy=> MmDwTY5pcWKrdHnvckBw\iC{ZXPvcYJqdmGwdDDGS2ZTOSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDiZYN2dG:4aYL1d{Bqdm[nY4Tl[EBqdnOnY4SgZ4VtdHNidYPpcochT0eJR2HES2tFYUmYTGDJJIF{KHO3YoP0doF1\SCjZoTldkAyKHSxIESgbJJ{KGK7IITpcYUuemW|b3z2[YQh\my3b4Lld4NmdmOnIHHzd4F6NCCLQ{WwQVAvODB6zszN MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODVyM{mzPEc,OzB3MEO5N|g9N2F-
NCI-H1703 MUDGeY5kfGmxbjDhd5NigQ>? Mnu0NVAhfU1? NX\5Z4x5OjRiaILz MmXZTY5pcWKrdHnvckBw\iCWTlnLJIlvKGi3bXHuJG5EUS2KMUewN{Bk\WyuczD0doFve2[nY4Tl[EB4cXSqIHzlcpRqfmm{YXygeoVkfG:{IEfUSnAh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIH;mJGdUUzNiaX7obYJqfG:{IGigZYN1cX[jdHXkJHRPUUtvbXXkbYF1\WRiV370M3RETi:kZYThMYNifGWwaX6t[IVx\W6mZX70JJRz[W6|Y4LpdJRqd25iYYSgNVAhfU1iYX\0[ZIhOjRiaILzJIJ6KGy3Y3nm[ZJie2VicnXwc5J1\XJiYYPzZZk> MlnKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVIzQDl{Lze+R4hGVUKOPD;hQi=>
LoVo M{TrXGN6fG:2b4jpZ4l1gSCjc4PhfS=> MW[xNEB2VQ>? NYH1e4JOPzJiaILz M3PLWmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KFewdD;i[ZRiNWOjdHXubY4he2mpbnHscIlv\yCmZYDlcoRmdnRiaIXtZY4hVG:YbzDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjdDCxNEB2VSCjZoTldkA4OiCqcoOgZpkhSVSSbHn0[UBie3OjeR?= M4DyWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUzOjh7Mj:nQmNpTU2ETEyvZV4>
HCT116 MnT1R5l1d3SxeHnjbZR6KGG|c3H5 NVvwWXFqOTBidV2= NH7BT3A4OiCqcoO= NE\zSo9EgXSxdH;4bYNqfHliYXfhbY5{fCCZboSvZoV1[S2lYYTlcolvKHOrZ37hcIxqdmdiZHXw[Y5l\W62IHj1cYFvKEiFVEGxOkBk\WyuczDhd5Nme3OnZDDhd{Bk\WyuII\pZYJqdGm2eTDheEAyOCC3TTDh[pRmeiB5MjDodpMh[nliQWTQcIl1\SCjc4PhfS=> MmD5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVIzQDl{Lze+R4hGVUKOPD;hQi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
CDK1 / p-CDK1 / p53 / p21 ; 

PubMed: 24238094     


(A) Dovitinib induces phosphorylation of CDK1(Tyr15) in nasopharyngeal carcinoma cells. HONE1 cells were incubated with Dovitinib (5 μM) and harvested at the indicated time-points. Lysates were prepared and the indicated proteins were detected with immunoblotting. Equal loading of lysates was confirmed by immunoblotting for actin. (B) Dovitinib induces phosphorylation of CDK1Tyr15 in HeLa cells. HeLa cells were exposed to the indicated concentrations of Dovitinib for 24 hrs. Lysates were prepared and analysed with immunoblotting. Equal loading of extracts was accessed by immunoblotting of actin. (C) Dovitinib induces phosphorylation of CDK1Tyr15 in Hep3B cells. Hep3B cells were treated with the indicated concentrations of Dovitinib for 24 hrs. Lysates were prepared for immunoblotting analysis. Actin was probed to confirm equal loading. 

p-PDGFR-β / PDGFR-β / p-ERK / ERK ; 

PubMed: 23228017     


Phosphorylation of p-PDGFR-β and p-ERK were inhibited by dovitinib at pharmacologically relevant concentrations in MHCC-97H and SMMC7721 cells.

p-VEGFR-2 / VEGFR-2 / p-FGFR-1 / FGFR-1 ; 

PubMed: 23228017     


Dovitinib inhibited the phosphorylation of FGFG-1, VEGFR-2, and downstream ERK in HMVEC and HUVEC endothelial cells at pharmacologically relevant concentrations.

p-STAT3 / STAT3 / Mcl-1 / LC3 / Beclin 1 / p62 ; 

PubMed: 31485222     


The protein extracts from dovitinib-treated were subjected to immunoblot analysis for p-STAT3, STAT3, Mcl-1, beclin1, LC3B, p62, and actin.

24238094 23228017 31485222
Growth inhibition assay
Cell viability; 

PubMed: 28467797     


Cell viability of peripheral blood mononuclear cells (PBMCs) and RPMI8226 cells treated with dovitinib in RPMI1640 medium containing 5% FBS for 24 h. Data are presented as mean±SD. Experiments were performed in triplicate.* P < 0.01, **P < 0.001 versus control.

28467797
体内研究 在KMS-11移植鼠模型中,按鼠体重,每千克处理60 mg Dovitinib,导致FGFR3的衰退,结果肿瘤生长抑制率达到94%。[1] 在SCID-NOD 鼠中,Dovitinib作用于MV4;11肿瘤时显示出强的抗癌活性。[2] Dovitinib也有效抑制能激活FGFR3的KMS-11肿瘤。[4]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

体外激酶实验:

在体外研究时,Dovitinib溶解在DMSO中,浓度达到20mM,在实验使用前用培养基稀释。FGFR3, FGFR1, PDGFR-β, 和VEGFR1-3的激酶域在含有如下物质的混合物中测定。混合物包含50 mM HEPES (pH 7.0), 2 mM MgCl2, 10 mM MnCl2,1 mM NaF, 1 mM DTT (二硫苏糖醇), 1 mg/mL BSA (牛血清清蛋白), 0.25 µM 生物肽段基质(GGGGQDGKDYIVLPI), 1到30 µM ATP (加量取决于酶的Km值)。测定c-KIT 和FLT3的反应,调节PH到7.5,先加入0.25 到1 µM生物肽段基质(GGLFDDPSYVNVQNL),然后加入0.2到 8 µM ATP。反应在室温下温育1到4小时,磷酸化的肽段移到含有封闭缓冲液(含25 mM EDTA和50 mM HEPES, pH 为7.5),且包被链霉亲和素的微量滴定板上。使用回归曲线计算IC50值。
细胞实验:[1]
- 合并
  • Cell lines: B9细胞及多发性骨髓瘤细胞(Y373C, G384D, K650E,和J807C)
  • Concentrations: 400 nM 左右
  • Incubation Time: 72小时
  • Method: MTT实验测细胞活力,B9细胞及多发性骨髓瘤细胞按5x103或20x103密度接种在96孔板上。细胞加入30 ng/mL aFGF和100 µg/mL肝素或者1% IL-6 ,及Dovitinib 温育72小时,然后测定细胞活力。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 右侧腹皮下注射KMS-11细胞的雌性BNX 鼠
  • Dosages: 10, 30,或60 mg/kg
  • Administration: 饲喂处理
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 30 mg/mL (76.44 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
30% PEG400+0.5% Tween80+5% propylene glycol
30 mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 392.43
化学式

C21H21FN6O

CAS号 405169-16-6
储存条件 粉状
溶于溶剂
别名 CHIR-258

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02268435 Withdrawn Drug: dovitinib plus imatinib Gastrointestinal Stromal Tumors Asan Medical Center March 2015 Phase 1
NCT01700270 Completed Drug: dovitinib (TKI258)|Drug: fluvoxamine Advanced Solid Tumors Excluding Breast Cancer Novartis Pharmaceuticals|Novartis May 2013 Phase 1
NCT01680796 Withdrawn Drug: Dovitinib|Drug: Bortezomib|Drug: Dexamethasone Multiple Myeloma University of Florida|Novartis Pharmaceuticals February 2013 Phase 1
NCT01266070 Terminated Drug: Dovitinib Von Hippel-Lindau Syndrome M.D. Anderson Cancer Center|Novartis November 2012 Phase 2
NCT01515969 Terminated Drug: Erlotinib hydrochloride|Drug: Dovitinib lactate Non-small Cell Lung Cancer (NSCLC) Recurrent|Non-small Cell Lung Cancer (NSCLC) Stage IV Heather Wakelee|Genentech Inc.|Novartis|Stanford University July 2012 Phase 1

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

FLT3 Signaling Pathway Map

FLT3 Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID